P70377 (FGF13_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fibroblast growth factor 13
Short name=FGF-13

Alternative name(s):
Fibroblast growth factor homologous factor 2
Short name=FHF-2

Gene names

Name:	Fgf13
Synonyms:	Fhf2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, may participate to the refinement of axons by negatively regulating axonal and leading processes branching. Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus. Ref.8 Ref.9 Ref.10 Ref.11 Isoform 1 seems not to be involved in neuroblast polarization and migration but regulates axon branching. Ref.8 Ref.9 Ref.10 Ref.11 May regulate voltage-gated sodium channels transport and function. Ref.8 Ref.9 Ref.10 Ref.11 May also play a role in MAPK signaling. Ref.8 Ref.9 Ref.10 Ref.11
Subunit structure	Interacts with SCN8A; may regulate SCN8A activity By similarity. Interacts with SCN1A; may regulate SCN1A activity By similarity. Interacts with SCN5A; the interaction is direct and may regulate SNC5A density at membranes and function. Interacts with MAPK8IP2; may regulate the MAPK8IP2 scaffolding activity. Ref.8 Ref.10
Subcellular location	Cell projection › filopodium. Cell projection › growth cone. Cell projection › dendrite. Nucleus Ref.7 Ref.10 Ref.11. Cytoplasm Ref.7 Ref.10 Ref.11. Note: Not secreted. Localizes to the lateral membrane and intercalated disks of myocytes. Ref.7 Ref.10 Ref.11 Isoform 1: Nucleus Ref.7 Ref.10 Ref.11. Isoform 2: Cytoplasm Ref.7 Ref.10 Ref.11.
Tissue specificity	Detected in brain, eye and heart. In brain, the different isoforms display different patterns of expression. Expressed in brain and heart (at protein level). Isoform 3 is highly expressed in cardiac myocytes while isoform 1 is the most abundant in brain. Ref.2 Ref.7 Ref.10
Developmental stage	Expressed in the subplate of the embryonic cortex and the axonal tracts in the intermediate zone, and in axonal tracts of projection neurons, specifically in the corticothalamic tract and the corpus callosum (at protein level). Isoform 2 is transiently expressed in the neocortex and hippocampus from E17 to P7 (at protein level). In embryonic brain, present in all divisions of the central and peripheral nervous system and it is at least 5 times more abundant than other FHFs. Detected in the subplate, ganglionic eminences, and proliferative zones of the cortical wall at E14. Detected in the cortical plate of the cerebral cortex, hippocampus, and striatum from E17 to P14. Expression is markedly reduced in adult brain where it is most abundant in hippocampus. Also detected in developing kidney. Ref.2
Post-translational modification	May be phosphorylated By similarity.
Disruption phenotype	Conditional knockout mice lacking fgf13 in the cerebral cortex or mice lacking fgf13 in most tissues display similar phenotypes of impaired spatial acquisition and memory. The cued memory and the capacity of novel object recognition are altered. They also display anxiety-related and reduced depression-like behaviors. This is associated with a disorganization of cortical structure and neural circuits. The laminar formation of the neocortex is delayed and the hippocampal development is also affected. Ref.11
Sequence similarities	Belongs to the heparin-binding growth factors family.

Ontologies

Keywords
Biological process	Neurogenesis
Cellular component	Cell projection Cytoplasm Microtubule Nucleus
Coding sequence diversity	Alternative splicing
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: Compara cerebral cortex cell migration Inferred from mutant phenotype Ref.11. Source: UniProtKB establishment of neuroblast polarity Inferred from mutant phenotype Ref.11. Source: UniProtKB hippocampus development Inferred from mutant phenotype Ref.11. Source: UniProtKB learning Inferred from mutant phenotype Ref.11. Source: UniProtKB memory Inferred from mutant phenotype Ref.11. Source: UniProtKB microtubule polymerization Inferred from mutant phenotype Ref.11. Source: UniProtKB negative regulation of collateral sprouting Inferred from mutant phenotype Ref.11. Source: UniProtKB negative regulation of microtubule depolymerization Inferred from mutant phenotype Ref.11. Source: UniProtKB neuron migration Inferred from mutant phenotype Ref.11. Source: UniProtKB protein localization to plasma membrane Inferred from mutant phenotype Ref.10. Source: UniProtKB
Cellular_component	axon Inferred from direct assay Ref.11. Source: UniProtKB cytoplasm Inferred from direct assay Ref.11. Source: UniProtKB dendrite Inferred from direct assay Ref.11. Source: UniProtKB filopodium Inferred from direct assay Ref.11. Source: UniProtKB growth cone Inferred from direct assay Ref.11. Source: UniProtKB intercalated disc Inferred from direct assay Ref.10. Source: UniProtKB microtubule Inferred from direct assay Ref.11. Source: UniProtKB nucleus Inferred from direct assay Ref.11. Source: UniProtKB plasma membrane Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	beta-tubulin binding Inferred from direct assay Ref.11. Source: UniProtKB microtubule binding Inferred from direct assay Ref.11. Source: UniProtKB protein kinase activator activity Inferred from electronic annotation. Source: Compara sodium channel regulator activity Inferred from mutant phenotype Ref.10. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: P70377-1)

Also known as: FGF13A; mFHF-2(1S); FGF13-S;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P70377-2)

Also known as: FGF13B; mFHF-2(1U); FGF13-U;

The sequence of this isoform differs from the canonical sequence as follows:
     1-62: MAAAIASSLIRQKRQAREREKSNACKCVSSPSKGKTSCDKNKLNVFSRVKLFGSKKRRRRRP → MALLRKSYS

Isoform 3 (identifier: P70377-3)

Also known as: FGF13-VY; mFHF-2(1Y+1V);

The sequence of this isoform differs from the canonical sequence as follows:
     1-63: MAAAIASSLI...SKKRRRRRPE → MSGKVTKPKE...HHKENTEPEE

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 245	245	Fibroblast growth factor 13		PRO_0000147608
Regions
	Region	1 – 62	62	Mediates targeting to the nucleus
	Region	67 – 201	135	Mediates interaction with sodium channels By similarity
	Region	157 – 164	8	Tubulin-binding domain necessary and sufficient for tubulin-binding
Natural variations
	Alternative sequence	1 – 63	63	MAAAI…RRRPE → MSGKVTKPKEEKDASKVLDD APPGTQEYIMLRQDSIQSAE LKKKESPFRAKCHEIFCCPP KQVHHKENTEPEE in isoform 3.		VSP_044130
	Alternative sequence	1 – 62	62	MAAAI…RRRRP → MALLRKSYS in isoform 2.		VSP_044131
Experimental info
	Sequence conflict	2	1	A → T in AAB18918. Ref.1
	Sequence conflict	2	1	Missing in AAB71606. Ref.2
	Sequence conflict	199	1	L → Q in AAB71606. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (FGF13A) (mFHF-2(1S)) (FGF13-S) [UniParc]. Last modified October 3, 2012. Version 2. Checksum: 5B96D41AC3A3DF78	FASTA	245	27,588
	10 20 30 40 50 60 MAAAIASSLI RQKRQARERE KSNACKCVSS PSKGKTSCDK NKLNVFSRVK LFGSKKRRRR 70 80 90 100 110 120 RPEPQLKGIV TKLYSRQGYH LQLQADGTID GTKDEDSTYT LFNLIPVGLR VVAIQGVQTK 130 140 150 160 170 180 LYLAMNSEGY LYTSEHFTPE CKFKESVFEN YYVTYSSMIY RQQQSGRGWY LGLNKEGEIM 190 200 210 220 230 240 KGNHVKKNKP AAHFLPKPLK VAMYKEPSLH DLTEFSRSGS GTPTKSRSVS GVLNGGKSMS HNEST
	Isoform 2 (FGF13B) (mFHF-2(1U)) (FGF13-U) [UniParc]. Checksum: 7736A3671677B263	FASTA	192	21,605
	10 20 30 40 50 60 MALLRKSYSE PQLKGIVTKL YSRQGYHLQL QADGTIDGTK DEDSTYTLFN LIPVGLRVVA 70 80 90 100 110 120 IQGVQTKLYL AMNSEGYLYT SEHFTPECKF KESVFENYYV TYSSMIYRQQ QSGRGWYLGL 130 140 150 160 170 180 NKEGEIMKGN HVKKNKPAAH FLPKPLKVAM YKEPSLHDLT EFSRSGSGTP TKSRSVSGVL 190 NGGKSMSHNE ST
	Isoform 3 (FGF13-VY) (mFHF-2(1Y+1V)) [UniParc]. Checksum: E0EAE1C9DFFBE0EA	FASTA	255	28,760
	10 20 30 40 50 60 MSGKVTKPKE EKDASKVLDD APPGTQEYIM LRQDSIQSAE LKKKESPFRA KCHEIFCCPP 70 80 90 100 110 120 KQVHHKENTE PEEPQLKGIV TKLYSRQGYH LQLQADGTID GTKDEDSTYT LFNLIPVGLR 130 140 150 160 170 180 VVAIQGVQTK LYLAMNSEGY LYTSEHFTPE CKFKESVFEN YYVTYSSMIY RQQQSGRGWY 190 200 210 220 230 240 LGLNKEGEIM KGNHVKKNKP AAHFLPKPLK VAMYKEPSLH DLTEFSRSGS GTPTKSRSVS 250 GVLNGGKSMS HNEST

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Fibroblast growth factor (FGF) homologous factors: new members of the FGF family implicated in nervous system development." Smallwood P.M., Munoz-Sanjuan I., Tong P., Macke J.P., Hendry S.H., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J. Proc. Natl. Acad. Sci. U.S.A. 93:9850-9857(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Eye.
[2]	"Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective tissue and heart." Hartung H., Feldman B., Lovec H., Coulier F., Birnbaum D., Goldfarb M. Mech. Dev. 64:31-39(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Spinal ganglion.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Eye.
[7]	"Isoform diversity among fibroblast growth factor homologous factors is generated by alternative promoter usage and differential splicing." Munoz-Sanjuan I., Smallwood P.M., Nathans J. J. Biol. Chem. 275:2589-2597(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-98 (ISOFORM 3), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[8]	"Fibroblast growth factor homologous factors are intracellular signaling proteins." Schoorlemmer J., Goldfarb M. Curr. Biol. 11:793-797(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MAPK SIGNALING, INTERACTION WITH MAPK8IP2.
[9]	"Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase." Schoorlemmer J., Goldfarb M. J. Biol. Chem. 277:49111-49119(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MAPK SIGNALING.
[10]	"Fibroblast growth factor homologous factor 13 regulates Na+ channels and conduction velocity in murine hearts." Wang C., Hennessey J.A., Kirkton R.D., Wang C., Graham V., Puranam R.S., Rosenberg P.B., Bursac N., Pitt G.S. Circ. Res. 109:775-782(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN SODIUM CHANNEL REGULATION, TISSUE SPECIFICITY, INTERACTION WITH SCN5A, SUBCELLULAR LOCATION.
[11]	"Fibroblast growth factor 13 is a microtubule-stabilizing protein regulating neuronal polarization and migration." Wu Q.F., Yang L., Li S., Wang Q., Yuan X.B., Gao X., Bao L., Zhang X. Cell 149:1549-1564(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEURON POLARIZATION, FUNCTION IN NEURON MIGRATION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TUBULIN-BINDING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U66202 mRNA. Translation: AAB18918.1. AF020737 mRNA. Translation: AAB71606.1. AK141848 mRNA. Translation: BAE24857.1. AL669891, AL672247, AL713968 Genomic DNA. Translation: CAM19176.1. AL713968, AL672247 Genomic DNA. Translation: CAM22824.1. AL713968, AL672247 Genomic DNA. Translation: CAM22825.1. AL713968, AL669891, AL672247 Genomic DNA. Translation: CAM22827.1. AL672247, AL713968 Genomic DNA. Translation: CAM27417.1. AL672247, AL713968 Genomic DNA. Translation: CAM27418.1. AL672247, AL669891, AL713968 Genomic DNA. Translation: CAM27420.1. CH466583 Genomic DNA. Translation: EDL42180.1. CH466583 Genomic DNA. Translation: EDL42182.1. BC018238 mRNA. Translation: AAH18238.1. AF199608 mRNA. Translation: AAF31395.1.
IPI	IPI00108285. IPI00311361. IPI00405439. IPI00606472.
RefSeq	NP_034330.2. NM_010200.2.
UniGene	Mm.7995.
3D structure databases
ProteinModelPortal	P70377.
SMR	P70377. Positions 64-212.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000033473.
PTM databases
PhosphoSite	P70377.
Proteomic databases
PaxDb	P70377.
PRIDE	P70377.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033473; ENSMUSP00000033473; ENSMUSG00000031137. ENSMUST00000119306; ENSMUSP00000113206; ENSMUSG00000031137.
GeneID	14168.
KEGG	mmu:14168.
UCSC	uc009tht.2. mouse. uc009thu.2. mouse.
Organism-specific databases
CTD	2258.
MGI	MGI:109178. Fgf13.
Phylogenomic databases
eggNOG	NOG308177.
GeneTree	ENSGT00700000104040.
HOGENOM	HOG000290676.
HOVERGEN	HBG007580.
InParanoid	P70377.
KO	K04358.
OrthoDB	EOG4VQ9Q2.
Gene expression databases
CleanEx	MM_FGF13.
Genevestigator	P70377.
GermOnline	ENSMUSG00000031137. Mus musculus.
Family and domain databases
InterPro	IPR008996. Cytokine_IL1-like. IPR002209. GF_heparin-bd. IPR002348. IL1_HBGF. [Graphical view]
PANTHER	PTHR11486. PTHR11486. 1 hit.
Pfam	PF00167. FGF. 1 hit. [Graphical view]
PRINTS	PR00263. HBGFFGF. PR00262. IL1HBGF.
SMART	SM00442. FGF. 1 hit. [Graphical view]
SUPFAM	SSF50353. Cytok_IL1_like. 1 hit.
PROSITE	PS00247. HBGF_FGF. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	FGF13. mouse.
NextBio	285320.
SOURCE	Search...

Entry information

Entry name

FGF13_MOUSE

Accession

Primary (citable) accession number: P70377
Secondary accession number(s): B1AU21 , O35338, Q3UR31, Q8VCY9, Q9JLA5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 3, 2012
Last modified:	May 29, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program